title: Genetic mechanisms of tumor suppression by the human p53 gene.
abstract: Mutations of the gene encoding p53, a 53-kilodalton cellular protein, are found frequently in human tumor cells, suggesting a crucial role for this gene in human oncogenesis. To model the stepwise mutation or loss of both p53 alleles during tumorigenesis, a human osteosarcoma cell line, Saos-2, was used that completely lacked endogenous p53. Single copies of exogenous p53 genes were then introduced by infecting cells with recombinant retroviruses containing either point-mutated or wild-type versions of the p53 cDNA sequence. Expression of wild-type p53 suppressed the neoplastic phenotype of Saos-2 cells, whereas expression of mutated p53 conferred a limited growth advantage to cells in the absence of wild-type p53. Wild-type p53 was phenotypically dominant to mutated p53 in a two-allele configuration. These results suggest that, as with the retinoblastoma gene, mutation of both alleles of the p53 gene is essential for its role in oncogenesis.
authors.affiliation: Department of Pathology, School of Medicine, University of California, San Diego, La Jolla 92093-0612.
authors.forename: P L
authors.initials: PL
authors.lastname: Chen
authors.forename: Y M
authors.initials: YM
authors.lastname: Chen
authors.forename: R
authors.initials: R
authors.lastname: Bookstein
authors.forename: W H
authors.initials: WH
authors.lastname: Lee
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002934:Cinnamates; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics*; D005822:Genetic Vectors; D006801:Humans; D006921:Hygromycin B / Q000031:analogs & derivatives; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000235:genetics; D009154:Mutation; D009355:Neomycin; D012516:Osteosarcoma / Q000235:genetics*; D010957:Plasmids; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D002934:Cinnamates; D006921:Hygromycin B; C026273:hygromycin A; D004247:DNA; D009355:Neomycin